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PMID: 11865069 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore.

Molecular and cellular biology ·Vol. 22 ·No. 6 ·2002-03-00 ·Pages 1926-35

Risso A, Braidot E, Sordano MC, Vianello A, Macrì F, Skerlavaj B, Zanetti M, Gennaro R, Bernardi P

Abstract

BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes. In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria. The effect of the peptide was synergistic with that of Ca(2+) and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore. The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release. We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ. Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.

MeSH Terms
Animals Anti-Infective Agents/pharmacology Antimicrobial Cationic Peptides/pharmacology Calcium/metabolism,pharmacology Cattle Cell Death/drug effects Cells, Cultured Cyclosporine/pharmacology Cytochrome c Group/metabolism Dose-Response Relationship, Drug Fluoresceins/metabolism Fluorescent Dyes Humans Immunity, Innate/physiology Ion Channels K562 Cells Leukocytes, Mononuclear/cytology,drug effects,metabolism Membrane Potentials/drug effects Membrane Proteins/drug effects,metabolism Mitochondria/drug effects,metabolism Mitochondrial Membrane Transport Proteins Mitochondrial Permeability Transition Pore Proteins/pharmacology U937 Cells
Chemicals
Anti-Infective Agents Antimicrobial Cationic Peptides BMAP-28 Cytochrome c Group Fluoresceins Fluorescent Dyes Ion Channels Membrane Proteins Mitochondrial Membrane Transport Proteins Mitochondrial Permeability Transition Pore Proteins Cyclosporine Calcium fluorexon
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Risso Angela
Department of Biotechnology and Biomedical Sciences, University of Udine, via Cotonificio 108, I-33100 Udine, Italy. angela.risso@dbea.uniud.it
Braidot Enrico
Sordano Maria Concetta
Vianello Angelo
Macrì Francesco
Skerlavaj Barbara
Zanetti Margherita
Gennaro Renato
Bernardi Paolo
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.6.1926-1935.2002
Email
angela.risso@dbea.uniud.it
Published
2002-03-00
Pages
1926-35
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC135593
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.6.1926-1935.2002 PMC Full Text View journal details
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